Efficacy of Antimicrobials in Young Children with AOM

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DESCRIPTION (provided by applicant): A "watchful waiting" approach for children with acute otitis media (AOM) has been the standard of care for 10 years in several European countries for children as young as 6 months of age. However, most reports endorsing watchful waiting are based on meta-analyses which include trials characterized by numerous and serious methodological limitations. AOM management guidelines jointly developed by the American Academy of Pediatrics and the American Academy of Family Physicians endorsed this "watchful waiting" approach in children 6-24 months with non-severe disease and uncertain diagnosis and in children >24 months with non-severe disease regardless of certainty of diagnosis. It remains unclear to what extent antimicrobial treatment is of benefit in young children with AOM, irrespective of the severity of their illness. It may be the case either that the "watchful waiting" approach might safely be extended to include children aged 6-23 months with severe illness and/or certain diagnosis, or on the other hand, that even children with nonsevere illness would benefit sufficiently from antimicrobial treatment to justify its use. The proposed study is designed to overcome the methodological problems of earlier studies and to address this important public health issue in the group of children (6-23 months of age) who experience the greatest impact of this common condition. 264 children will be enrolled in a randomized, placebo-controlled, double-blind clinical trial to be conducted by validated otoscopists at Children's Hospital of Pittsburgh and at an affiliated pediatric practice. Primary outcome will be assessed at the early on-therapy visit (Day 4-5) and will compare the clinical efficacy of amoxicillin-clavulanate vs. placebo. Secondary outcomes to be compared between treatment groups include: (1) clinical efficacy at the end-of-therapy visit (Day 10-12), (2) symptom burden (using 3 global scales) during each of the first 7 days of therapy and at study visits, (3) proportion of children who develop worsening symptoms before 72 hours of medication, (4) quantity of analgesic medication administered by children's parents, (5) adverse events, (6) effects on nasopharyngeal bacterial colonization, (7) tympanometric outcomes, (8) direct and indirect medical costs, and (9) parental satisfaction with therapy. We assume a minimum overall clinical cure rate of 85% for children treated with amoxicillin-clavulanate. Accordingly, a total of 120 evaluable children per treatment group will allow detection of a 15% difference from placebo (85% vs. 70%), with 80% power at a significance level of 0.05 (two-tailed). This carefully designed clinical trial in children 6-23 months will address an issue of particular concern that has not been satisfactorily addressed in previous studies, whether antimicrobial treatment along with analgesic treatment offers young children with AOM an earlier and more complete overall clinical improvement (including relief of discomfort) than analgesic treatment alone. This earlier and more complete improvement may constitute the most important benefit of antimicrobial treatment.